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AlphaFill
AlphaFill is an algorithm based on sequence and structure similarity that 鈥渢ransplants鈥?missing compounds to the AlphaFold models. By adding the molecular context to the protein structures, the models can be more easily appreciated in terms of function and structure integrity.
ID:75186UploaderBioTreasury
2023.03.12
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Abstract
Artificial intelligence-based protein structure prediction approaches have had a transformative effect on biomolecular sciences. The predicted protein models in the AlphaFold protein structure database, however, all lack coordinates for small molecules, essential for molecular structure or function: hemoglobin lacks bound heme; zinc-finger motifs lack zinc ions essential for structural integrity and metalloproteases lack metal ions needed for catalysis. Ligands important for biological function are absent too; no ADP or ATP is bound to any of the ATPases or kinases. Here we present AlphaFill, an algorithm that uses sequence and structure similarity to 'transplant' such 'missing' small molecules and ions from experimentally determined structures to predicted protein models. The algorithm was successfully validated against experimental structures. A total of 12,029,789 transplants were performed on 995,411 AlphaFold models and are available together with associated validation metrics in the alphafill.eu databank, a resource to help scientists make new hypotheses and design targeted experiments.
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AlphaFill: enriching AlphaFold models with ligands and cofactors
Maarten L. Hekkelman,Ida de Vries,Robbie P. Joosten,Anastassis PerrakisNature Methods2022
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Proteins & Proteomes
Protein structure analysis
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